Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5856508 | Regulatory Toxicology and Pharmacology | 2015 | 10 Pages |
Abstract
rAd5-hTERTC27, a replication-defective adenovirus vector carrying hTERTC27, has been proposed for possible use against hepatocellular carcinoma (HCC). In this study, we investigated the long-term toxicity of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys. rAd5-hTERTC27 was administered intravenously once a week for 13Â weeks followed by a one-month recovery period. As of 4Â months, all animals displayed overall good health. Anti-adenoviral antibodies emerged in a dose-independent manner. The levels of complement components, C3 and C4, in the rAd5-hTERTC27 middle-dose and high-dose groups and C4 in the rAd5-EGFP group increased significantly after the 2nd treatment in monkeys. Slight-mild pathological changes of the liver occurred only in the rAd5-hTERTC27 high-dose group (2/16) in rats and not in any other group in either rats or monkeys. With the increase of the dose, the incidence of lymphocyte depletion in the spleen of rats and reactive hyperplasia of the splenic corpuscle in monkeys increased. However, the changes in the liver and spleen were reversible. Given the above data, intravenous administration of rAd5-hTERTC27 (up to 4Â ÃÂ 1010Â VP/kg in rats and 0.9Â ÃÂ 1010Â VP/kg in monkeys) appears to be well-tolerated, providing support for its potentially safe use in clinical trials for the treatment of HCC.
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Authors
Pei-jian Yue, Lei He, Qing-yu Shen, Shu-wei Qiu, Xiao-ming Rong, Han-xian Gong, Ying Peng,